The proposed experiments will attempt to reveal the molecular architecture of retinal components (photoreceptor and pigment epithelium membranes) in a minimally denatured and minimally extracted state by high resolution electron microscopy. Using cryo-microtomy procedures in parallel with a new non-denaturing chemical fixation protocol, we will attempt to ascertain the following data: What is the in vivo molecular organization of photoreceptor membranes? What is the function of the cytoplasmic domain of rhodopsin? What is the locus of non-rhodopsin proteins in photoreceptor membranes? What are the cyclic molecular morphological changes which occur during shedding? What is the fate of lipid in photoreceptor outer segments when tissue is never exposed to fixation or organic solvents? Such studies should provide valuable information on the molecular interplay between the pigment epithelium and photoreceptors and further our understanding of the structural basis of normal photoreceptor function.